During the development of a primary culture of chromaffin cells from adrenals of adult rats, we observed that the 2 month old cultured chromaffin cells extended neurites spontaneously if culture medium was not changed for a week. The result seems to imply that trophic material may be produced and accumulated in the culture medium of the chromaffin cells. Further studies on this observation now suggest that neurite promoting activity exists in conditioned medium from the adrenal chromaffin cells in culture. This neurite promoting factor was found to be protein in nature because it was inactivated by heating at 100 degrees and trypsin digestion. It is likely that this trophic activity is not due to NGF, fibroblast growth factors, epidermal growth factor, or insulin like growth factor. Neuropeptides, VIP, NPY, head activator peptide and motilin were all found to exert no effect on neurite out-growth from the cultured chromaffin cells. The exact nature of the trophic material detected in this study awaits further characterization. The proposed course of this study is to further characterize the putative trophic material detected in the culture medium of rat adrenal chromaffin cells. The study will include development of a new technique to detect and isolate a small quantity of trophic material.